Transdermal nicotine patch (TN) has been shown to boost quit rates above those achieved with behavioral counseling alone, yet the majority of smokers do not maintain abstinence. A nicotine nasal spray (NS) with reinforcing properties more similar to smoking has been approved for clinical use, and has shown success rates at least comparable to TN. Because of possible irritant effects of NS, it may not be the preferred treatment for all smokers. To date there have been no empirically validated methods to match smokers to a particular treatment. We believe that smokers who derive greater positive reinforcement from smoking will benefit more from NS versus TN., and further, that such smokers can be identified by their genotypes for genes important in dopamine regulation. As an extension of our ongoing research on dopamine genes and smoking, we propose to evaluate whether genetic and non-genetic factors can be used to predict the relative efficacy of NS versus TN. Further, we will explore whether the effects of genotype on smoking cessation are mediated by nicotine replacement and/or by heritable personality traits. In the proposed randomized clinical trial, smokers will receive behavioral counseling plus either NS or TN. After initial eligibility screening, subjects will complete a pretreatment assessment of smoking related and psychological variables and have blood drawn for genotyping and cotinine analysis. NS and TN will be delivered over an 8 week treatment period. All subjects will also participate in 8 1.5 sessions of group behavioral counseling. mediating outcomes will be assessment at pretreatment (e.g., smoking reinforcement, novelty-seeking personality) and prior to subsequent treatment visits (e.g., mood, withdrawal). Smoking outcomes will be assessed prior to each treatment visit and at 8 weeks, 6 months, and 12 months after the target quit data (biochemically verified). The overall goal of this research is to increase our understanding of the role of genetic and psychological factors in response to NRT. Further, we will learn more about why people fail to quit smoking by studying the bio-behavioral mechanisms of genetic effects. The ultimate objective is to provide information necessary to tailor smoking treatment with NS versus TN to individual smokers' needs.